Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001054836 | SCV001219191 | uncertain significance | Neurofibromatosis, type 1 | 2019-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 2217 of the NF1 protein (p.Phe2217Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002365707 | SCV002662223 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-08-22 | criteria provided, single submitter | clinical testing | The p.F2217L variant (also known as c.6651C>A), located in coding exon 44 of the NF1 gene, results from a C to A substitution at nucleotide position 6651. The phenylalanine at codon 2217 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |